Endokrinologie最新文献

A-, B- and D cells of the pancreas were found to be innervated. Moreover, at one and the same insular cell numerous and extended synapses are formed with very small synaptic clefts (less than 20 nm). It is ultrahistochemically detectable that A- and B cells are likewise sympathetically (adrenergically) innervated. Including specific data from the literature, the insular cell apparatus must be regarded as a organ which is highly controlled by the nervous system.

The production of androgens and progesterone by dispersed gerbil interstitial cells was studied in vitro. Incubation of 80,000-100,000 cells with 2.3-143.8 microIU LH/vial resulted in a 1.9-8.0 fold increase of androgen and in a 2.2-19.8 fold increase of progesterone release. The ratio of androgens/progesterone released by gerbil interstitial cells was 8.1 in the absence of LH, and was significantly higher in the presence of 143.8 microIU LH/vial (17.7). In all cell assays performed (n = 5), a highly significant positive correlation between LH-stimulated androgen and progesterone release was found. In comparison with androgen biosynthesis in vitro in either the rat or mouse, gerbil, interstitial cells are much more sensitive to LH as argued from both androgen and progesterone release. The reason for this high responsiveness of gerbil interstitial cells is not clear; it may be due in part to the very low bioactive LH levels in gerbils leaving a major part of LH receptors unoccupied thus allowing even trace amounts of LH to fully activate steroidogenesis.

In two from 3 hyperkalemic patients with chronic glomerulonephritis associated with suppressed aldosterone production ("selective hypoaldosteronism") fractional free water excretion increased and urine osmolality decreased during sodium (Na) restriction. In one of the patients with severe renal concentrating defect in combination with partial vasopressin deficiency polyuria was paradoxically accentuated by lowered Na intake. Na restriction induced 1. a dramatic increase in plasma aldosterone levels, 2. a decrease in glomerular filtration rate associated with a marked disturbance in the glomerulotubular balance resembling to the effects of volume expansion, and 3. a decrease in urinary arginine vasopressin excretion. Paradoxical enhancement of water excretion was explained by increased delivery of filtrate into the distal nephron, increased abstraction of Na from the tubular fluid together with insufficient water permeability of the collecting tubules and lowered vasopressin production.

An enzyme immunoassay for the measurement of 17-hydroxyprogesterone (OHP) is described. The antigens, OHP-3-CMO-BSA and 11-deoxycortisol-21-hemisuccinate-BSA have been used to produce antisera in rabbits. The enzyme marker was horseradish peroxidase. Bound/free separation was achieved by the double antibody/polyethylene glycol method. The method was used for plasma samples, capillary blood dried on paper disc and for saliva. The normal values for OHP in newborns and children were determined. This method makes possible a selected screening program for congenital adrenal hyperplasia in the newborns.

To estimate the role of hypothalamus and hypophysis in the development of functional activity of pancreas, the changes of reactivity of pancreatic B-cells to glucose resulting from encephalectomy and decapitation of fetuses were investigated. Reactivity of pancreas was determined by the changes of insulin secretion induced by the addition of glucose into incubation medium. It was found that, when hypophysis and hypothalamus were removed as a result of decapitation of fetuses from normal or from diabetic pregnant rats on days 17.5-18.5 of development, their pancreas remained insensitive to glucose on 21.5 day. Removal of hypothalamus only when fetuses were encephalectomized on day 17.5 of development also resulted in the loss of sensitivity of fetal pancreas to glucose. Injection of hypothalamus homogenate to encephalectomized fetuses restored the stimulating effect of glucose on B-cells. When pancreas fragments of decapitated fetuses were preincubated together with adenohypophyses of adult rats, the decapitation effect was eliminated, and an increase of glucose concentration in the medium caused an intensive release of insulin. Similar restoring effect was induced by growth hormone (GH) and adrenocorticotrophin (ACTH) when used in in vivo and in vitro experiments. The data obtained give evidence of a possible contribution of hypothalamus and hypophysis to the control of the development of functional activity of pancreas in rat prenatal ontogenesis. However, the mechanism of this regulation remains unclear yet.

Administration of a low dose of estradiol (0.25 or 2.5 microgram/animal) to immature rats caused a pulsatile receptor translocation, resulting in a single nuclear receptor peak (1-3 hr) and maintenance of the uterine growth until 24 hr. At a higher dose (10.0 microgram/rat), maintaining the circulatory estradiol levels for a longer duration, a biphasic nuclear translocation occurred. The usual profile of nuclear receptor binding until 12 hr was followed by a second phase of receptor translocation, resulting in an additional nuclear receptor peak at 24 hr. The uterus continued to grow until 72 hr, reaching five times its original wet weight. The duration of receptor interaction and the magnitude of uterine stimulation would, therefore, appear to be largely dependent upon the period of bioavailability of estradiol. However, there are additional intracellular regulatory mechanisms not fully understood as yet, which seem to modulate the cytosol-nuclear receptor dynamics, thus influencing the extent of uterine stimulation.

Progestin (medroxyprogesterone acetate, trade name Depo-Provera, Upjohn, Belgium) in 6 body-weight-matched doses with those used in women, i.e., 0.05 mg/mouse, given intramuscularly at 4-5-day intervals (duration of one ovulation) induced a marked reduction of fertility with precocious atresia of Graafian follicles, minimal numbers of growing follicles and an excess of corpora lutea; the lymphoid system remained morphologically and functionally normal. A combination of progestin and androgen (testosterone isobutyrate, trade name Agovirin Depot Biotika, Czechoslovakia) in a total dose of 1 mg + 0.9 mg (body-weight-matched with that used in men) or one order higher and divided into 6 doses given at 17-day intervals, i.e. roughly one half of the duration of spermatogenesis, had no inhibitory effect on spermatogenesis, whereas higher doses damaged the lymphoid system. This damage was reflected in a markedly reduced thymus weight with great depletion of cortex lymphocytes and diminished capacity for antibody formation to sheep red blood cells. The significance of the immunosuppressive effect for estimating the risks involved in the administration of sex steroids in human contraception is discussed.

Plasma vasopressin (AVP) and oxytocin (OXT) were determined by radioimmunoassay in healthy young men before, during and after a running exercise until exhaustion. In four of the five test subjects (one subject was underloaded) physical load resulted in a marked increase in plasma AVP with peak values of 11.7 to 57.8 pg/ml at exhaustion. Plasma OXT increased in three test subjects with peak values of 4.5 to 23.9 pg/ml. Within 1 h of recovery, both neuropeptides returned to basal plasma levels. The relationship between plasma AVP and osmolality (p less than 0.001) suggests that changes in osmolality play a dominant role in regulating the secretion of AVP. Besides peripheral effects, the increased levels of AVP and/or OXT during and immediately after the exercise, respectively, might induce a favourable action on the brain function. Determination of plasma AVP and OXT during a day-night cycle in the same test subjects reveals increased AVP levels from 02.00 to 08.00 h as compared to the other time periods chosen (18.00--24.00 h, p less than 0.001; 08.00--16.00 h, p = 0.031). In contrast, OXT does not differ between these time periods but decreased from 08.00 to 16.00 h (p less than 0.01). Accordingly, no correlation exists between both neuropeptides suggesting an independent secretion. It is unclear whether the circadian variations shown are able to influence the neuropeptide response to exercise.

Patients with a history of idiopathic calcium oxalate stones but without current stone formation do not react to stimulation of parathyroid extract as expected after high dose calcium pretreatment. With Ca2+ pretreatment, these patients show higher serum and also renally generated levels of cAMP after rapid injection of extreme parathyroid extract-concentrations. Healthy controls show a modest increase of serum levels cAMP after similar stimulation with parathyroid extracts. In contrast to patients, calcium pretreatment of controls significantly decreases the renal cAMP response to parathyroid extract stimulation. Without Ca2+ pretreatment, both patients and controls show a strong increase in urinary and also in renally generated cAMP levels following parathyroid extract stimulation.

(--)-Hydroxycitrate is a well-known inhibitor of the citrate cleavage enzyme (EC 4.1.3.8). In isolated hepatocytes it inhibits fatty acid synthesis from glucose, but it does not affect fatty acid synthesis from acetate. In its presence, insulin stimulates and glucagon inhibits incorporation of labelled acetate into fatty acids. This is evidence that both hormones directly influence fatty acid synthesis from acetate.